"Gene-to-drug" is a new paradigm in drug discovery based on the novel methodology of chemical genomics. This approach provides a means to systematically analyze the vast quantities of genomics information generated by high throughput experiments to develop new pharmacophores. The methodology seeks to match biological targets and drug candidates by establishing information feedback loops to associate genes and compounds. This proposal envisions a novel molecular informatics analysis method to correlate biological information such as gene expression patterns with activity profiles of therapeutic agents to extract molecular-level information on cellular mechanisms. Expected outcomes of the proposed research are: 1) development of a novel informatics methodology to link gene expressions and structural features of compounds; 2) a unique database containing experiments results from direct testing of the effects of compound treatment on gene expression patterns for various cell lines. Phase II will focus on the further development of informatics software and accompanying database. This product will find widespread use by medicinal and pharmaceutical chemists in the identification of potential pairs of compound classes and specific gene subsets, and will also help determine the cellular pathways for molecular-level manipulation of pharmacology so that novel cancer therapeutics can be discovered. PROPOSED COMMERCIAL APPLICATIONS: The proposed research will result in two commercial products: (1) a database of the effects of various compounds on gene expression levels; (2) a novel bioinformatics software tool for identifying chemical features within compounds that are responsible for specific compound-gene or compound-protein interactions.